ORIGINAL RESEARCH

XEN� Gel Stent in Medically Refractory Open-AngleGlaucoma: Results and Observations After One Yearof Use in the United States

Andrew G. Kalina . Paul H. Kalina . Morgan M. Brown

Received: April 16, 2019 / Published online: June 13, 2019� The Author(s) 2019

ABSTRACT

Introduction: The purpose of this study was toevaluate intraocular pressure (IOP) loweringand safety of XEN� stent in medically refrac-tory, progressive, open-angle glaucoma (OAG).Methods: Forty-seven eyes of 42 patients weretreated with XEN� stent alone or combinedwith phacoemulsification.Results: Mean IOP decreased from 22.34 ±

7.34 mmHg to 12.91 ± 4.21, 12.95 ± 4.36,13.49 ± 3.91, and 13.36 ± 3.63 mmHg at 1, 3,6, and 12 months (95% confidence interval [CI][20.24, 24.44], [11.71, 14.12], [11.63, 14.27],[12.36, 14.62], and [12.10, 14.62]), respectively.Mean number of medications decreased from2.96 ± 1.20 (95% CI [2.62, 3.30]) at baseline to0.75 ± 1.27 (95% CI [0.31, 1.19]) at 1 year. At

1 year (n = 32), complete success was achievedin 68.8% (n = 22/32) (i.e., IOP reduction C 20%and IOP\ 18 mmHg without medication orany secondary glaucoma intervention). Quali-fied success was achieved in 90.6% (n = 29/32)(i.e., IOP reduction of C 20% and IOP\18 mmHg with and without medication orany secondary glaucoma intervention). Eleveneyes had not yet reached 12 months. Twopatients (three eyes) died before 1 year; onepatient (one eye) was lost to follow up. Adverseevents: localized choroidal hemorrhage in oneeye; hypotony (IOP\6 mmHg) at day 1 in 10eyes, with full resolution by 2 weeks. No per-sistent hypotony or maculopathy occurred.Stent erosion with removal occurred in twoeyes. Fourteen eyes (29.8%) underwent need-ling. One patient required trabeculectomy.Conclusions: XEN� stent is effective and rela-tively safe surgery for medically refractory,progressive, OAG out to 1 year. Intraocularpressure and medications were significantlyreduced.

Keywords: Glaucoma, MIGS; Surgery; XEN�

stent

INTRODUCTION

Glaucoma is the world’s leading cause ofblindness [1]. The disease consists of a painless,progressive optic neuropathy leading to the

Enhanced digital features To view enhanced digitalfeatures for this article go to https://doi.org/10.6084/m9.figshare.8209919.

A. G. KalinaEastern Virginia Medical School, 825 FairfaxAvenue, Norfolk, VA, USA

P. H. Kalina (&)Department of Ophthalmology, Park NicolletClinic, 3900 Park Nicollet Boulevard, St. Louis Park,MN, USAe-mail: paul.kalina@parknicollet.com

M. M. BrownDepartment of Statistics, HealthPartners Institute,8170 33rd Avenue South, Bloomington, MN, USA

Ophthalmol Ther (2019) 8:435–446

https://doi.org/10.1007/s40123-019-0192-8

death of optic nerve fibers and correspondingloss of visual field. Untreated or inadequatelycontrolled glaucoma commonly results in sev-ere vision loss, which has a tremendoussocioeconomic impact [1]. Numerous clinicaltrials have shown that lowering intraocularpressure (IOP) halts glaucoma progression [2–4]and, in doing so, prevents vision loss andmaintains quality of life.

Medication, laser trabeculoplasty, and tra-beculectomy are all effective treatments forlowering IOP. First-line management is com-monly either medication or laser. Rates ofnoncompliance with medication vary widely,from 5% to 80% [5]. Noncompliance is associ-ated with both poor outcomes and high healthcare costs [6–10]. In addition, chronic use oftopical glaucoma medications causes inflam-mation and alteration of the conjunctival sur-face [5].

Laser trabeculoplasty is used as either pri-mary or add-on therapy. Laser cannot achieveIOP below episcleral venous pressure, and itseffect wanes with time, at a failure rate of nearly10%/year [11–13].

Glaucoma surgery is indicated in eyes inwhich IOP is refractory to laser or medicalmanagement, disease progression occurs despitesuch therapy, or medication side effects orintolerance preclude their use. Trabeculectomyand tube shunt surgery are the most commonsurgical procedures for glaucoma. Althoughtube shunt surgery has gained popularity, it hasnot replaced trabeculectomy as the gold stan-dard for surgically lowering IOP. These proce-dures are both done ab externo and requiresignificant disruption of conjunctiva andTenon’s capsule, increasing the risk of scar for-mation and surgical failure [14, 15]. Standard-ization and regulation of aqueous outflow aredifficult and are associated with a relativelyhigh percentage of short- and long-term com-plications, including persistent hypotony, ser-ous choroidal detachments, suprachoroidalhemorrhage, bleb leaks, infection, cataract, andhypotony maculopathy [14, 16–18].

Minimally invasive glaucoma surgery (MIGS)has become popular due to the desire for safer,quicker, less invasive yet effective surgicalalternatives to trabeculectomy and tube shunt

surgery. Compared with current approaches,MIGS procedures are characterized by minimaltissue disruption, ab interno insertion, short-ened surgical time, and IOP lowering. Less sur-gery should translate to fewer sight-threateningcomplications [19]. With U.S. Food and DrugAdministration (FDA) approval in November2016, the XEN� gel stent became the first MIGSoption available in the United States for treat-ment of refractory, progressive, open-angleglaucoma (OAG) and also did not require com-bination with cataract surgery. The stent pro-cedure is an alternative to trabeculectomy forprogressive, uncontrolled glaucoma. The stentis a 6-mm hydrophilic, noninflammatory,nondegrading porcine gelatin stent [20]. It isthe world’s first ab interno MIGS approach thatmodels standard trabeculectomy by shuntingaqueous humor from the anterior chamber tothe subconjunctival space through theobstructed trabecular meshwork. Both proce-dures create an external filtration bleb and relyon adjunct antifibrotic agents to enhance fil-tration success. However, insertion of the XEN�

stent requires no conjunctival dissection, andfiltration blebs are typically lower-lying andmore diffuse than those seen with trabeculec-tomy [20–29].

The flow characteristics of the XEN� gel stentare based on the Hagen-Poiseuille equation,which defines the amount of resistance tolaminar fluid flow through a cylindrical tube[20]. Thus, the rate of aqueous humor flowthrough the XEN� stent is determined by stentlength and inner diameter. During productdevelopment, 45 lm was found to be the opti-mal diameter to prevent hypotony yet maxi-mize aqueous outflow for long-term IOP control[22, 24–27].

Although the XEN� gel stent has been usedand studied in countries outside the UnitedStates, data from within the United States arelimited. We therefore undertook this study toevaluate the efficacy and safety of the stent bothas a standalone filtration procedure and incombination with cataract surgery for patientswith progressive OAG refractory to medicaltherapy. In studying this device, we hoped tobetter understand how to optimize success andidentify potential issues with placement or

436 Ophthalmol Ther (2019) 8:435–446

postoperative management to assist glaucomasurgeons as XEN� stent use becomes morewidespread.

METHODS

Study Population

This was an investigator-initiated, prospective,noncomparative study of glaucoma patientsreferred within Park Nicollet Clinic, a multi-specialty, non-university medical practice in St.Louis Park, Minnesota, USA. Eligible patientsenrolled in the study were 21 years or older withsevere-stage OAG that was uncontrolled,refractory to medical therapy, and requiringeither trabeculectomy or tube shunt surgery tohalt glaucoma progression. Uncontrolled,medically refractory OAG was defined asuncontrolled IOP, documented visual fieldprogression, and/or increasing optic nervedamage despite maximum medical therapy(four or more topical IOP-lowering medications,or fewer in the case of tolerability or efficacyissues) and laser treatment, when possible.Patients with mild or moderate-stage OAG werenot included in the study, as other MIGS devi-ces were available for eyes with these stages ofdisease. Of the FDA-approved MIGS devices, theXEN� stent is the only one that utilizes thesubconjunctival space and the only one thatcan achieve intraocular pressure lowering to thesame level as standard trabeculectomy or tubeshunt surgery. Unlike the other categories ofMIGS, the FDA approved use of the XEN� stentwith or without cataract surgery.

All procedures performed in studies involv-ing human participants were in accordancewith the ethical standards of the HealthPartnersInstitute Institutional Review Boards and withthe 1964 Helsinki declaration and its lateramendments or comparable ethical standards.Informed consent was obtained from all par-ticipants in the study for both the procedureitself and inclusion in the study. TheHealthPartners Institutional Review Boardapproved this study.

Preoperatively, eyes underwent a completeophthalmic examination, including slit-lamp

and funduscopic examinations, Goldmannapplanation tonometry (two separate measure-ments, with resetting of the dial to 10 mmHgbetween readings), gonioscopy, corneal pachy-metry, standardized automated perimetry, andoptical coherence tomography analysis.Patients were required to have healthy, free, andmobile conjunctiva superiorly in the area ofplanned XEN� stent implantation and an openangle with a visible trabecular meshwork.Exclusion criteria included previous incisionalglaucoma filtration or tube surgery, conjuncti-val pathology, aphakia, epithelial downgrowth,anterior chamber intraocular lens, presence ofvitreous in the anterior chamber, and the fol-lowing types of glaucoma: uveitic, neovascular,angle-closure, iridocorneal endothelial syn-drome, and Axenfeld-Rieger syndrome.

At minimum, postoperative examinationswere conducted at day 1, week 1, and months 1,3, 6, and 12. Each visit included slit-lamp andposterior segment examinations, IOP by Gold-mann applanation tonometry, and gonioscopy.Standardized automated perimetry was per-formed at 1 year at minimum. Endothelial cellcounts were not measured pre- or postopera-tively. Visual acuity, medications, and adverseevents were also recorded.

Surgical Implantation

Surgeries were performed from March 2017 toMay 2018 by a single surgeon (PK). All surgerieswere performed under topical anesthesia. Afterprepping and draping the eye in sterile oph-thalmic fashion, the superior nasal conjunctivawas marked 3 mm from the limbus in theplanned exit point of the stent. Using a 30Gneedle, 0.1 ml of mitomycin-C (0.2 mg/ml) wasinjected posteriorly into Tenon’s capsule. Usingcellulose sponges, the mitomycin-C was mas-saged over the area of anticipated stent place-ment, with efforts to keep it away from thelimbus. Main and side port incisions were cre-ated. A combination of cohesive and dispersiveviscoelastic was used to fill the anterior cham-ber. In patients with cataract surgery, preserva-tive-free lidocaine was injected before theviscoelastic. Phacoemulsification and lens

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implantation were performed before XEN�

stent placement. The angle was inspected beforeXEN� stent insertion with a disposable gonio-prism (Katena, Denville, NJ, USA). Afterobtaining the XEN� stent inserter, the protec-tive devices were removed and the inserter waschecked to confirm that it contained a stent.The inserter was introduced into the eyethrough the main incision, and the needle wasdirected across the anterior chamber towards 12o’clock. Countertraction was supplied by usinga Vera hook (Katena) in the side port. Thegonioprism was then reapplied to ensure thatthe inserter was positioned to engage the anglejust anterior to the trabecular meshwork.

The inserter needle was then slowly pushedthrough the sclera until the needle was seenexiting into the subconjunctival space close tothe preoperative markings and, ideally, aboveTenon’s capsule. The needle was then rotatedtowards 12 o’clock. Engagement of the bluelever, which advances and releases the XEN�

stent, occurred next, followed by slowadvancement. Subsequent slow retraction of theinserter needle resulted in stent placement intothe subconjunctival space. The injector wasthen removed from the eye. Stent positioning inthe subconjunctival and anterior chamber stentwas confirmed. Tissue or stent manipulationwas rarely needed after insertion. Automatedirrigation/aspiration was used to remove theviscoelastic from the eye. While doing so, thepresence of a bleb superiorly was confirmed.The incisions were hydrated with a balancedsalt solution and, where needed, sutured with10-0 nylon.

Follow-Up Examinationsand Postoperative Management

Glaucoma medications were continued untilthe day of surgery. A washout period was notincluded. After XEN� gel stent implantation, allglaucoma medications were stopped in theoperative eye. Postoperative examinations wereperformed on day 1, week 1, and months 1, 3, 6,and 12. Additional postoperative visits werescheduled in between these time points, asdictated by the clinical findings. Topical

antibiotics were used four times a day for1 week. Topical steroids were used four times aday for 1 month, then tapered over 4 weeks.Restarting of glaucoma medications, blebneedling, 5-fluorouracil (5-FU) injections, orother interventions were done at the discretionof the surgeon.

Needling and 5-FU Injections

Clinical exam findings determined if and whenneedling and 5-FU were to be done. Mostcommonly, eyes had elevated IOP with signs ofdecreasing bleb function (i.e., lack of micro-cysts, vascularization, and Tenon’s encapsula-tion, scarring in and around the external tip ofthe stent). Needling was performed undermicroscopic guidance in a minor procedureroom. Betadine, antibiotic, and 2% lidocainewere topically applied. A solution of 2% lido-caine, 0.1 ml, was then injected subconjuncti-vally temporally, and cotton-tipped applicatorswere used to disperse the lidocaine to the loca-tion of the external stent. Under sterile condi-tions, an angled 27G needle was directedtowards the external end of the stent and sur-rounding fibrosis. Using the tip of the needle,the fibrous adhesions surrounding the externalend of the stent were lysed, and an attempt wasmade to raise the stent above the episcleral andscleral surface. On completion of the procedure,0.1 ml of 5-FU (50 mg/ml) was injected tempo-rally, and additional antibiotic drops wereinstilled. Subconjunctival injections of mito-mycin could not be used due to institutionalregulatory policies. Both topical antibiotic andsteroid drops were prescribed four times a day.The antibiotic was stopped at 7 days and thesteroid tapered over 4 weeks.

Outcome Measures

Measurements included IOP, medications, andcomplications. Degree of success was defined byWorld Glaucoma Association guidelines, whichwere also used for data presentation [30].Complete success was defined as an IOP reduc-tion of C 20% and an IOP of\18 mmHgwithout medication or any secondary glaucoma

438 Ophthalmol Ther (2019) 8:435–446

intervention. Qualified success was defined asan IOP reduction of C 20% and anIOP\18 mmHg with and without medicationor any secondary glaucoma intervention. Eyeswith follow-up that were in neither of thesegroups were deemed failures.

Statistical Analysis

Data analysis was performed using R 3.4.1 sta-tistical software. The IOP was analyzed by cal-culating various descriptive statistics, includingrange, median, and mean. The standard devia-tion, standard error, and 95% CI were computedaround the mean. The change in IOP frompreoperative measurements to each of the sub-sequent time points was also examined. Theresultant values were reported as both anumeral and a percentage. These analyses werereplicated for various subsets of the data,including XEN� stent standalone proceduresversus XEN� stent with cataract surgery. Tovisualize the data, the following plots werecreated: (1) combined graph showing mean IOPchange, percentage change of mean IOP, andmean medication reduction values from base-line over time, and (2) scatterplots of preoper-ative and postoperative IOP for 6 months and12 months.

The above descriptive statistics were alsocalculated for the raw observed medication usevalues and the change in medication from pre-operative measurements at the study timepoints. These computations were carried out forthe overall study group, the standalone XEN�

stent eyes, and the combined XEN� stent andcataract surgery eyes. A Wilcoxon test waschosen to analyze our data. This nonparametrictest was chosen over a t test because our datafailed the normality assumption.

RESULTS

Forty-seven eyes of 42 patients with medicallyrefractory OAG with visual field and/or opticdisc progression underwent XEN� stent inser-tion (as a standalone procedure or in combina-tion with phacoemulsification) from April 2017to May 2018. Demographic and baseline

characteristics for the patients are displayed inTable 1. The mean age of the study populationwas 78.15 ± 8.55 years (54–91 years). Allpatients were white, except for one Asianpatient. Regarding the different subtypes ofglaucoma, most eyes had primary OAG (n = 32;68.1%), with the remainder being pseudoexfo-liative (n = 11; 23.4%) and low-tension glau-coma (n = 4; 8.5%). Glaucoma staging wassevere in all 47 eyes (100%). Patient follow-upwas available on 46 eyes at 1 week, 47 eyes at1 month, 42 eyes at 3 months, 46 eyes at6 months, and 32 eyes at 12 months. Eleveneyes have not yet reached the 12-month follow-up time point. Two patients (three eyes) diedduring the study period before reaching their12-month visit. One patient (one eye) was lostto follow-up at 12 months.

After XEN� stent implantation, the meanchange in IOP (Fig. 1) was-13.12 ± 8.42 mmHg,-11.40 ± 8.24, -9.43 ± 8.02 mmHg, -9.38 ±

7.77, -8.75 ± 7.16, and -8.45 ± 7.33 mmHg at1 day, 1 week, and 1, 3, 6, and 12 months,respectively (95% CI [10.71, 15.52], [9.02, 13.78],[7.13, 11.72], [7.03, 11.73], [6.68, 10.82], and[5.91, 10.99]). Percentage change in IOP frombaseline for all eyes (Fig. 1) was 55% ± 27%,47% ± 27%, 37% ± 26%, 36% ± 27%, 34% ±

24%,and33% ± 24%at1 day, 1 week, and1,3, 6,and 12 months, respectively (95%CI [47%, 62%],[39%, 54%], [29%, 44%], [28%, 45%], [27%, 41%],and [25%, 41%]). Scatterplots for preoperativeand postoperative IOP are shown for 6-month(Fig. 2) and 12-month (Fig. 3) data. On each plot,the line shows the best fit.

IOP data for standalone XEN� stent versuscombined XEN� stent with cataract surgery areshown in Table 2. The small number of eyes ineach group prevented meaningful statisticalinterpretation between groups.

The mean number of medications at baselineand change after surgery at each time point forthe total population are shown in Fig. 1. Atbaseline, 97.9% of eyes (n = 46) were receivingat least one glaucoma medication. Side effectsor ineffectiveness limited the number of glau-coma medications in some eyes. A statisticallysignificant reduction in medications occurred,from 2.96 ± 1.20 (95% CI [2.62, 3.30]) at

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baseline to 0.75 ± 1.27 (95% CI [0.31, 1.19]) at1 year.

At 6 months (n = 46), complete success wasachieved in 82.6% (n = 38/46), qualified successin 97.8% (n = 45/46), and failure in 2.2% (n = 1/46). For eyes with 1-year follow-up (n = 32),complete success was achieved in 68.8%(n = 22/32), qualified success in 90.6% (n = 29/32), and failure in 9.4% (n = 3/32). Eleven eyeshad not yet reached 12-month follow-up. Twopatients (three eyes) died before reaching 1-yearfollow-up, and one patient (one eye) was lost tofollow-up.

Adverse Events

Intraoperatively, one eye (2.1%) had a small,nonexpulsive choroidal hemorrhage that self-resorbed without issue. At 1 month, two stents(4.3%) in different patients were noted to haveeroded through the conjunctiva, which neces-sitated immediate stent removal. A detailedreview of both eyes was conducted. In each eye,XEN� stent insertion was uneventful, withdesired placement above Tenon’s capsule andunderneath the conjunctiva. Mitomycin dosingand tissue manipulation were per study

Table 1 Demographics and baseline characteristics of thetotal population (n = 42)

Parameter Total: 47 eyes of 42patients

Age (years)

Mean ± SD 78.15 ± 8.55

Range 54–91

Sex, n (%)

Female 28 (66.7%)

Male 14 (33.3%)

Study eye, n (%)

Right 20 (42.6)

Left 27 (57.4)

Ethnicity, n (%)

White 41 (97.6%)

Asian 1 (2.4%)

Hispanic or Latino 0

Black/African American 0

Glaucoma type, n (%)

POAG 32 (68.1)

Pseudoexfoliative 11 (23.4)

Low tension 4 (8.5)

Previous glaucoma procedures

Selective laser trabeculoplasty,

n (%)

20 (42.6)

iStent, n (%) 1 (2.1)

Endocyclophotocoagulation,

n (%)

1 (2.1)

Filtration or tube surgery,

n (%)

0

IOP at baseline

Mean ± SD 22.34 (7.34)

Range 11.00–36.00

Mean medications at baseline,

n (SD)

2.96 (1.20)

Table 1 continued

Parameter Total: 47 eyes of 42patients

Total number, n (%)

None 1 (2.1)

One 3 (6.4)

Two 10 (21.3)

Three 22 (46.8)

Four 7 (14.9)

Five or more 4 (8.5)

XEN� stent and cataract

surgery, n (%)

27 (57.4)

XEN� stent as standalone,

n (%)

20 (42.6)

Phakic, n (% of 20) 7 (35)

Pseudophakic, n (% of 20) 13 (65)

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protocol. In the early postoperative period, eacheye had a single-digit IOP, diffuse bleb, slightlyshallow anterior chamber, and shallow serouschoroidals. At postoperative day 1, the externalportion of the stent was clearly visible; it wasstraight rather than angulated. However, in

each eye, the midsection of the stent bowedanteriorly and pressed against the outer wall ofthe conjunctival filtration bleb. This appearancepersisted throughout the entire month, despitechoroidal resolution and anterior chamber

Fig. 1 Mean intraocular pressure (IOP) change and meanmedication reduction from baseline for the overall popu-lation at each visit after XEN� stent placement.

?Percentage change in mean intraocular pressure (IOP)from baseline shown in parentheses

Fig. 2 Scatterplot of preoperative and postoperativeintraocular pressure (IOP) at 6 months. Line shows best fit

Fig. 3 Scatterplot of preoperative and postoperativeintraocular pressure (IOP) at 12 months. Line shows bestfit

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deepening. With the thinness of the conjunc-tiva overlying the stent and concern thatmanipulation might create a buttonhole, nei-ther stent was repositioned or redirected. Med-ications followed study protocol. Erosion wasnoted unexpectedly at the routine 1-monthvisit. Each eye was white and quiet. Neitherpatient reported any symptoms or new issues.Intraoperative stent removal was uneventful. Ineach eye, a second stent was inserted in a newlocation, away from the erosion. The secondstents functioned less optimally than the first,but neither eroded. Fortunately, neither eyedeveloped infection or vision loss from theerosion.

Hypotony (IOP\6 mmHg) was seen in 10eyes (21.3%) at day 1, with resolution in all eyesby 2 weeks. No hypotony, maculopathy,hyphema, endophthalmitis, anterior chamberflattening, cystoid macular edema, or perceivedmitomycin-related complications occurred.One eye (2.1%) required trabeculectomy. Noeyes showed significant loss in visual acuity dueto either the procedure or adverse events.

Fourteen of 47 eyes (29.8%) required need-ling and 5-FU injection 1–3 months postopera-tively. Needling was considered part of

procedure management and not an adverseevent, in agreement with another study [26].Our 29.8% needling rate is similar to that ofprevious studies by Hengerer et al. (27.7%) [26],Galal et al. (30.7%) [25], and Grover et al.(32.3%) [28]. Our rate was lower than thatreported by Fea et al. (50%) [31], Sheybani et al.(47%) [22], Schlenker et al. (43.2%) [29], andMansouri et al. (37%) [27]. Our study differedfrom Grover et al. [28], who inserted the XEN�

stent without conjunctiva disruption, butapplied mitomycin with a sponge after openingthe conjunctiva.

Optimal time for needling with trabeculec-tomy varies widely, depending on surgicaltechnique, surgeon preference, and patientpopulation [32, 33]. As with trabeculectomy,the reported average time of needling afterXEN� stent insertion also varied with Mansouriet al. (4.5 months) [27] and Hengerer et al. [26](1 week–3 months). In our study, needling wasperformed at 1–3 months, with improvement inIOP and bleb function in 10 of 14 eyes (71.4%).A second needling was performed in one eyewithout benefit.

No eyes showed significant loss in visualacuity due to either the procedure or adverse

Table 2 Mean IOP in eyes receiving XEN� stent as a standalone procedure (n = 20) versus XEN� stent with cataractsurgery (n = 27)

IOP (mmHg)

XEN� stentstandalone

95% confidenceinterval

XEN� stent with cataractsurgery

95% confidenceinterval

Baseline (mean ± SD) 24.18 ± 8.18

(n = 20)

(20.59, 27.76) 20.98 ± 6.47 (n = 27) (18.54, 23.42)

1 week post-op

(mean ± SD)

8.83 ± 4.13

(n = 20)

(7.01, 10.64) 12.79 ± 5.39 (n = 26) (10.72, 14.86)

1 month post-op

(mean ± SD)

11.83 ± 3.65

(n = 20)

(10.23, 13.42) 13.72 ± 4.48 (n = 27) (12.03, 15.41)

3 months post-op

(mean ± SD)

13.37 ± 5.11

(n = 19)

(11.07, 15.67) 12.61 ± 3.70 (n = 23) (11.09, 14.12)

6 months post-op

(mean ± SD)

13.53 ± 4.89

(n = 19)

(11.33, 15.73) 13.46 ± 3.14 (n = 27) (12.28, 14.65)

1 year post-op

(mean ± SD)

13.04 ± 4.50

(n = 14)

(10.68, 15.39) 13.61 ± 2.90 (n = 18) (12.27, 14.95)

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events. No observable corneal decompensationor other anterior segment issues related to theprocedure were noted during the study.Endothelial cell counts were not included inthis study.

DISCUSSION

Our prospective, noncomparative study foundXEN� gel stent surgery in eyes with and withoutconcomitant cataract surgery to be both effica-cious and relatively safe. The results of thisstudy based on reduction in IOP and medica-tion use compare favorably with publishedstudies on the XEN� gel stent. In a study withstandalone XEN� stent insertion, Grover et al.reported that 75.4% of patients obtained C 20%IOP lowering on similar or fewer medications at12 months [28]. In 49 eyes, Sheybani et al.reported 36.4% IOP reduction after 1 year, and89% achieved C 20% IOP lowering [22]. In astudy of 149 eyes, 62.1% of patients achievedC 20% IOP lowering, with a 71.1% success ratewhen defined by an IOP\ 16 mmHg (with orwithout medication) [27]. Galal et al. reported,on average, 23% IOP reduction at 1 year andC 20% IOP lowering without medication in42% of eyes [25]. Schlenker et al. found a 75%survival rate at about 10 months for completesuccess at an IOP B 21 mmHg [29]. At 1 year,Fea et al. found a 31.62% reduction in IOP and82.88% decrease in medication versus baseline[31]. Widder et al. reported a primary successrate (no revision) of 66% and overall success(limited to one revision) of 90% [34]. Hohbergeret al. reported a much lower complete successrate (defined as IOP\18 mmHg at any timepoint within 6 months of follow-up withoutlocal antiglaucomatous therapy or further sur-gical interventions), with 46.9% in single XEN�

gel stents and 53.3% in the combined XEN�

stent and cataract surgery group [35].In our study, the safety profile was favorable

overall. The postoperative complications thatmay occur with trabeculectomy or tube shuntsurgery, such as chronic hypotony, flat anteriorchamber, hyphema, hypotony maculopathy,kissing choroidal detachments, and bleb dyses-thesia, were not seen in this study. One

intraoperative, nonexpulsive choroidal hemor-rhage occurred, but caused no loss of vision.The two stent erosions (4.3%) resulted in noendophthalmitis or vision loss, but theiroccurrence stresses the importance of closelymonitoring eyes which have a XEN� stent.From previous studies, conjunctival erosion isan infrequent event [24–29, 34, 36]. The issuesthat did occur that might place eyes at higherrisk for erosion include failure to elevate thebleb above the implant, a too-short implantlength in the subconjunctival space, and themovement of the upper eyelid over the con-junctiva and implant. These factors did notseem to be the case in our two patients. Eacheye had a nicely elevated filtration bleb. How-ever, the midsection of the stent in each eye wasbowed, with slight pressure on the conjunctivalwall of the filtration bleb. This observation wasalso mentioned by Widder et al. [34]. Patientswith this clinical finding after XEN� stent sur-gery need to be monitored closely or have sur-gical revision [33]. Although our experience islimited to two eyes, the positioning did notcorrect or change over time; therefore, we rec-ommend that eyes with this postoperativefinding undergo early revision to avoid con-junctival erosion and the potentially vision-threatening complication of endophthalmitis.

The overall risk of erosion over time isunclear. The design of the XEN� stent makes itmuch less likely than tube shunts to erode. TheXEN� stent is 100 times more flexible than thesilicone tube shunt. In addition, the XEN� stenthas a much smaller outer diameter than a tubeshunt. Theoretically, these features reduce stresson surrounding tissues, with a resulting lowerlikelihood of erosion and migration. However,with ideal XEN� stent placement above Tenon’scapsule and just underneath the conjunctiva,the risk of erosion may be heightened. Thisissue is especially important to monitor,because older patients with glaucoma have thinconjunctiva and little Tenon’s capsule; topicalglaucoma medications alter the conjunctivalsurface, and the use of antifibrotic agents inhi-bit healing during and after surgery. Althoughno erosions were seen in eyes without a filteringbleb, this may be a problem in the future. Given

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the many factors involved in this issue, futurestudy is warranted.

Limitations

The study has several limitations. It was aprospective study, but it was also a noncom-parative analysis with no control group. Inaddition, the number of eyes is small. Nomedication washout was done at baseline;therefore, the unmedicated IOP is unknown. Arandomized controlled study with a largersample size and medication washout may yielddifferent results.

Because all but one patient was white, thisstudy cannot speak to the effectiveness orpotential issues with XEN� stent use in otherethnic populations such as African Americansand Hispanics. Neither can this study draw anyconclusions about XEN� stent effectivenessbased on age.

XEN� stent insertion is relatively straight-forward, but as with any surgical procedure,there is a learning curve. As we became moreexperienced, the stent functioned more favor-ably when positioned above Tenon’s capsule.Eyes with stent placement more intra-Tenon’scapsule tended towards higher IOPs and ahigher incidence of needling. Later eyes mayhave benefited from more ideal stent position-ing. Needling techniques and timing differamong glaucoma surgeons, making it difficultto reach standardized conclusions about thisprocedure. In this study, needling occurredwhen clinical exam results suggested restrictedaqueous flow. Because no needling took placeafter 3 months, it is unclear whether this pro-cedure would be beneficial at later stages.Because post-needling antifibrotic medicationwas limited to 5-FU injections, we cannotcomment on the effect of subconjunctival mit-omycin-C injections on filtrationenhancement.

Despite these study constraints, there islimited long-term data on the use of the XEN�

gel stent in the United States due to its relativelyrecent approval by the FDA. Thus, in spite of itslimitations, we hope that this study broadensawareness and knowledge of this new

treatment. In 12 months, the procedure hasshown effective IOP lowering, a significantreduction in glaucoma medications, and a rel-atively good safety profile. However, thepotential for conjunctival erosion exists, andwith the significant needling rate, surgeonsperforming the procedure need to be comfort-able with and knowledgeable about bleb man-agement. In summary, the data from this studysupport the XEN� gel stent as an effective, rel-atively safe, and less invasive surgical filtrationprocedure for patients with medically uncon-trolled glaucoma, either as a standalone proce-dure or combined with cataract surgery.

ACKNOWLEDGEMENTS

The authors sincerely thank all participants fortheir involvement in this study.

Funding. No funding or sponsorship wasreceived for this study or publication of thisarticle. The article processing charges werefunded by the authors.

Editorial assistance. Editorial assistanceand statistics support were supplied and fundedby Park Nicollet Clinic and HealthPartnersInstitute (Mary Van Beusekom, MS, ELS, MWCof HeathPartners Institute).

Authorship. All named authors meet theInternational Committee of Medical JournalEditors (ICMJE) criteria for authorship of thisarticle, take responsibility for the integrity ofthe work as a whole, and have given theirapproval for this version to be published.

Disclosures. Andrew G. Kalina, Paul H.Kalina, and Morgan M. Brown have nothing todisclose.

Compliance with Ethics Guidelines. Allprocedures performed in studies involvinghuman participants were in accordance withthe ethical standards of the HealthPartnersInstitute Institutional Review Boards and withthe 1964 Helsinki declaration and its lateramendments or comparable ethical standards.

444 Ophthalmol Ther (2019) 8:435–446

Informed consent was obtained from all par-ticipants in the study for both the procedureitself and inclusion in the study. TheHealthPartners Institutional Review Boardapproved this study.

Data availability. The data sets generatedand/or analyzed during the current study areavailable from the corresponding author onreasonable request.

Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommer-cial use, distribution, and reproduction in anymedium, provided you give appropriate creditto the original author(s) and the source, providea link to the Creative Commons license, andindicate if changes were made.

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